RABC

Browse

Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes

PMID	Title	PublicationDate	abstract
3760277	Oral methotrexate therapy for chronic rheumatoid arthritis ulcerations.	1986 Sep	Eight patients with long-standing rheumatoid arthritis and cutaneous vasculitis ulcerations resistant to conventional therapy were treated successfully with a low-dose intermittent regimen of oral methotrexate. Objective clinical response was prompt and complete resolution was observed at about 12 weeks of therapy. The drug was well tolerated. Mild gastrointestinal side effects were the most common untoward reaction. We conclude that methotrexate therapy is an effective agent for some of the extraarticular manifestations of rheumatoid arthritis including vasculitis, and further clinical evaluation should be a consideration.
2241282	Concentration and reactivity of the sulphydryl group population on the membrane of intact	1990 Sep	The sulphydryl population on erythrocyte membrane is shown to vary as a function of the nutritional status of the cell. When an assay based on reaction with Ellman's reagent and controlled conditions were used the mean values (SEM) for the sulphydryl population on the membranes of normal erythrocytes incubated overnight in the presence and absence of glucose were found to be 3.29 (0.27) and 2.56 (0.25) million sulphydryl functions per cell respectively. Under identical conditions rheumatoid erythrocytes incubated in the presence and absence of glucose were found to have a significantly lower sulphydryl population--1.54 (0.08) and 1.15 (0.08) million respectively. The predominant concentrations of sulphydryl groups on the membrane are found at sites on the transmembrane proteins and, in particular, on the hexose transport protein. By influencing the nutritional status of the cells significant differences in activity between the normal and diseased state have been identified and these may have a role in the aetiology of rheumatoid arthritis by altering the response of cells to oxidative stress.
3321380	Comparison of phenotype expression by mononuclear phagocytes within subcutaneous gouty top	1987	The mononuclear phagocyte infiltrate which occupies the gout tophus has been compared with that of the subcutaneous rheumatoid nodule. In the gout tophus, macrophage migration appears to be at a relatively low level and effectively terminates once these cells have been recruited into the corona. In the nodule the evidence suggests that both macrophage and granulocyte populations continuously migrate towards, and are progressively incorporated into, the necrotic centres. These observations indicate that chemotactic activity in rheumatoid nodules is at a higher level than in gout tophi, or that the rheumatoid mononuclear phagocyte is more responsive to such stimuli.
2084514	Expression of the collagenolytic and Ras-induced cysteine proteinase cathepsin L and proli	1990 Dec	Based on the observation that rheumatoid joint destruction is related to the presence of transformed-appearing proliferating synovial lining cells attached to cartilage and bone at the site of early destruction, we searched for the expression of proliferation- and transformation-associated oncoproteins in synovial tissues from patients with early destructive rheumatoid arthritis (RA). Immunolocalization of Ras and Myc proteins was found in about 70% of the RA cases and was restricted to the proliferating synovial lining cells. The cysteine proteinase, cathepsin L, which has been shown to be the major ras-induced protein in ras-transformed murine NIH 3T3 cells, was detected in 50% of the RA cases, predominantly in synovial cells attached to cartilage and bone at the site of joint destruction. Moreover, utilizing cytoplastic dot hybridization analysis, we demonstrated the presence of RNA sequences complementary to human cathepsin L in primary cultures of human synovial cells from RA joints and complementary to murine cathepsin L in synovial lining cells derived from MRL/l mice developing spontaneously a RA-like disease. Significant levels of ras oncogene transcripts and products in human RA synovial cells associated with an increased expression of the cathepsin L gene indicate that this collagen-degrading enzyme may contribute to the destruction of cartilage and bone in RA.
2339901	Immunological comparison of patients with rheumatoid arthritis with and without nephropath	1990 Apr	Serum immunoglobulins IgG, IgA, and IgM, serum complement components C3 and C4, circulating immune complexes, antinuclear antibodies, and rheumatoid factor were measured in 56 patients with rheumatoid arthritis (RA) and nephropathy (23 with mesangial glomerulopathy; 13 with membranous glomerulonephritis; and 20 with amyloidosis) and 35 patients with RA without nephropathy (controls). Renal immunofluorescence findings in patients with mesangial glomerulopathy were compared with the serologic data. There were no differences in the occurrence of rheumatoid factor, antinuclear antibodies, and circulating immune complexes and the concentrations of serum complement C3 and C4 between various RA nephropathy groups and controls. Serum IgA and IgM concentrations were significantly higher in patients with mesangial glomerulopathy and amyloidosis than in controls. In patients with mesangial glomerulopathy glomerular IgM, IgA, and C3 were the most prominent findings in immunofluorescence examination. The serum IgA concentration was significantly higher in those patients with mesangial glomerulopathy with mesangial IgA deposits than in those without (4.97 (SD 1.03) g/l v 2.07 (1.21) g/l). The highest serum IgA concentrations (5.08 (1.39) g/l) were seen in the four patients with IgA glomerulonephritis. The prevalence of IgA glomerulonephritis in the renal biopsy material of the patients with RA was 5%, which possibly differs little from that seen in the general population. The results suggest that circulating immune complexes may not have any major role in the pathogenesis of various nephropathy types in patients with RA, contrary to their role in most extra-articular manifestations of RA.
2259877	Introduction: B27-associated diseases.	1990	As an introduction, a hypothesis for the causation of ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and rheumatoid arthritis is outlined. It comprises ten basic mechanisms. With that hypothesis as a background, a further ten issues based on clinical evidence are presented for discussion. Finally, four questions are presented on behalf of the clinicians.
2357207	[Experiences with the Meuli total endoprosthesis of the wrist joint in patients with chron	1990 Jan	Artificial joint replacement of the wrist requires careful consideration of anatomic and mechanical factors as well as appreciation of the implant fixation techniques. This study presents experience with nine total wrist arthroplasties by the Meuli method in exclusively female patients after an average follow-up period of 7 8/12 years. On the basis of this evaluation and comparison to the results described by other authors cemented wrist prosthesis have shown an unacceptably high rate of failure especially because of loosening problems.
2003854	A double-blind study of deflazacort and prednisone in patients with chronic inflammatory d	1991 Mar	Deflazacort and prednisone were given to 26 patients with rheumatoid arthritis, polymyalgia rheumatica, or other chronic inflammatory diseases, in a double-blind study. Deflazacort rapidly and effectively suppressed disease activity in a manner supporting its assumed therapeutic potency of 83% that of prednisone. Prednisone induced a rapid increase in the level of daily calcium excretion that was not evident with deflazacort. Cortisol secretion was acutely inhibited by prednisone, but not by deflazacort. Neither corticosteroid had a significant effect on glucose metabolism, at the doses studied. Treatment with deflazacort may be an effective alternative to prednisone treatment, with fewer adverse effects on levels of calcium and cortisol, in patients with severe inflammatory conditions warranting the use of glucocorticoids.
3964314	Evaluation of arthritis self-management courses led by laypersons and by professionals.	1986 Mar	We compared the relative effectiveness of 2 arthritis patient education interventions. One intervention was modeled after that developed by Lorig, whereas the other had similar content but used health professionals rather than laypersons as instructors. Both interventions resulted in an increase in patients' knowledge of arthritis and in their use of exercise compared with a control group that received no intervention. However, neither intervention was any more effective than nonintervention in lessening patients' pain, improving their functioning, enhancing social support systems, lessening their depression, or improving their health behaviors beyond that of exercise. No differences in outcome measures were found between groups led by professional instructors and those led by lay instructors.
1717012	Local activation of lymphoid cells in rheumatoid synovium.	1991	Lymphoid cell phenotype was investigated in the peripheral blood, synovial fluid, and synovial tissue of sixteen patients with rheumatoid arthritis (RA). In the peripheral blood of RA patients the proportion of cells expressing HLA-DR and beta 2-microglobulin receptors was higher than in normal controls, whereas the proportion of cells that were CD5+ (i.e. were T lymphocytes) was lower. Expression of the other cell surface antigens studied remained in the normal range. In the synovial tissue and synovial fluid of RA patients there was an increased percentage of cells expressing HLA-DR, beta 2-microglobulin receptors, CD25, CD5, CD4, and Thy-1, but the proportion of CD8+ cells was significantly decreased compared with that seen in peripheral blood. The CD4+/CD8+ ratio in RA joints was therefore significantly higher than that in peripheral blood. The proportion of cells expressing HLA-DR correlated with disease activity.
2025306	Treatment of rheumatoid arthritis with monoclonal CD4 antibody M-T151. Clinical results an	1991 May	Recent experimental and clinical data point to the T helper lymphocyte subset as playing a central role in the pathogenesis of rheumatoid arthritis (RA). Thus, a therapeutic strategy aimed specifically at the CD4 T cell subset is warranted. We treated patients with active RA for 7 days with a daily dose of 20 mg of CD4 monoclonal antibody M-T151, administered intravenously over 30 minutes. There were no negative side effects. According to changes in the combined parameters of Ritchie articular index, pain assessment, grip strength, and morning stiffness, 6 patients had a good response. Clinical improvement was greatest approximately 2 weeks after termination of the therapy and lasted from 4 weeks to 6 months. Of the serologic parameters of inflammation, only the C-reactive protein level improved in the patients with a favorable response. Close immunologic monitoring revealed a transient, selective depletion of CD4+ T cells after each infusion. During the entire treatment period, residual circulating CD4+ cells were found to be coated with CD4 antibody, whereas free antibody was detected in the serum only for approximately 8 hours after each infusion. Immediately after infusion, soluble CD4 antigen appeared in the serum. In addition to the cell-bound CD4 antibody, complement components could be detected on the surface of the remaining CD4+ cells. The proliferative response of peripheral blood mononuclear cells to purified protein derivative was significantly diminished 4 weeks after cessation of antibody treatment. Six patients showed a weak antibody response to mouse immunoglobulin. In 4 of the responders who received a second course of therapy (2 of them as outpatients), a therapeutic effect was noted that was similar to that after the first course. Only 1 patient, who had low titers of serum IgE anti-mouse Ig antibodies, showed a mild anaphylactic reaction at the end of the second course of therapy. Treatment of RA with the monoclonal CD4 antibody M-T151 seems to be a promising alternative, although the optimal dose and the regimen of administration are still to be defined.
2114600	Complications of axial arthropathies.	1990 Jul	Involvement of the cervical spine by rheumatoid arthritis may have severe consequences secondary to subluxation, erosive changes, and soft-tissue inflammation. Unfortunately, the severity of radiographic findings may not directly correlate with the occurrence of cervical myelopathy. MRI has emerged as a noninvasive method of assessing the condition of the spinal cord and thecal sac as well as more precisely defining the nature of inflammatory soft-tissue changes that may result in bony erosion and cord compression. Ankylosing spondylitis is an arthropathy that classically involves the axial skeleton. Complications include acute fracture and pseudarthroses of the spine. Rarely, the development of a cauda equina syndrome has been reported. In addition to classic erosive arthropathies affecting the axial skeleton, ossification of the posterior longitudinal ligament may be associated with the development of severe myelopathy. A recently described type of amyloidosis characterized by beta-2 microglobulin deposition has been reported in patients on long-term hemodialysis. Bony erosion is seen in the spine in these patients. A causal relationship between beta-2 microglobulin and hemodialysis spondylarthropathy has yet to be definitely established.
1695517	Technique of dorsal synovectomy on the rheumatoid wrist.	1990	Synovectomy is the basic operation on the rheumatoid wrist. Dorsal synovectomy of the wrist is never performed in isolation. It is always combined with extensor tenosynovectomy, synovectomy of the distal radio-ulnar joint, and surgical stabilization of the wrist. Early wrist synovectomy is ideally performed when the disease is largely confined to the soft tissues and where the overall alignment of the wrist is preserved. Careful reconstruction of the soft tissues following synovectomy is paramount in maintaining or restoring wrist stability. The satisfactory long term results of early wrist synovectomy have encouraged an expansion of the indications particularly to include the more advanced cases. In such cases additional bony surgery can be combined with the synovectomy to allow the realignment and stabilization of the wrist, so avoiding, in the majority of cases, the need for arthroplasty or wrist fusion.
2462345	Structural and genetic features of human leukocytic antigen class II elements associated w	1988 Dec 23	Analysis of individual human leukocyte antigen (HLA) genes associated with rheumatoid arthritis was performed using oligonucleotide probes to identify putative susceptibility genes highly associated with disease. Among DR4-positive rheumatoid arthritis patients, two distinct DR-beta genes, Dw4 and Dw14, appear to be individual susceptibility alleles. Linked HLA genes at the DQ locus do not appear to contribute to this genetic risk. Among non-DR4 rheumatoid arthritis patients, a specific DNA sequence was identified that is shared by the Dw14 susceptibility gene and a majority of the non-DR4 rheumatoid arthritis patients. This sequence defines a specific small genetic element encoding a "Dw14 epitope" that appears to be a rheumatoid arthritis-associated risk factor indicative of a common genetic pathway in both DR4 and non-DR4-associated disease.
3539871	Ultrasonography in the study of pathological conditions of the hip.	1986 Jun	The authors describe the use of real-time ultrasonography in the investigation of the hip joint. The study involved 25 patients with traumatic, inflammatory or degenerative lesions. It was possible to evaluate effusion and capsular changes in 13 cases and to correlate these findings with the type of pathology involved. The ultrasonographic findings in the patients with degenerative or inflammatory joint disease were confirmed at operation. The method described is simple, quick and devoid of risk to the patient. It is therefore a useful investigation in the study of disorders of the hip joint.
3609658	Nonsteroidal antiinflammatory drug-induced intestinal inflammation in humans.	1987 Sep	This study examines the effects of nonsteroidal antiinflammatory drugs on the small intestine in humans. Using an 111In-leukocyte technique in patients with rheumatoid arthritis (n = 90) and osteoarthritis (n = 7), it appears that nonsteroidal antiinflammatory drugs cause small intestinal inflammation in two-thirds of patients on long-term treatment and on discontinuation, the inflammation may persist for up to 16 mo. The prevalence and magnitude of the intestinal inflammation was unrelated to the type and dose of nonsteroidal drugs and previous or concomitant second-line drug treatment. There was a significant inverse correlation (r = -0.29, p less than 0.05) between fecal 111In excretion and hemoglobin levels in patients treated with nonsteroidal antiinflammatory drugs. The kinetics of fecal indium 111 excretion in patients treated with nonsteroidal antiinflammatory drugs was almost identical to that of patients with small bowel Crohn's disease. Eighteen patients on nonsteroidal antiinflammatory drugs underwent a radiologic examination of the small bowel and 3 were found to have asymptomatic ileal disease with ulceration and strictures. Nineteen patients on nonsteroidal antiinflammatory drugs, 20 healthy controls, and 13 patients with Crohn's ileitis underwent a dual radioisotopic ileal function test with tauro 23 (75Se) selena-25-homocholic acid and cobalt 58-labeled cyanocobalamine. On day 4, more than half of the patients with rheumatoid arthritis had evidence of bile acid malabsorption, but the ileal dysfunction was much milder than seen in patients with Crohn's ileitis.
2058321	[Value of pepsinogen I in serum as a screening method for early detection of gastroduodena	1991 Jan	Gastroduodenal lesions of the mucosa are known to be the most frequent side effect during therapy with non-steroidal antiinflammatory drugs (NSAIDs). We investigated the radioimmunological determination of serum-pepsinogen I as an indicator for the quality of the gastroduodenal mucosa. A good correlation was found between the endoscopy findings of 78 patients and contemporary determinations of serum-pepsinogen. Further, a follow-up of pepsinogen I was made during the treatment of 107 patients with degenerative rheumatic diseases with eight different NSAIDs. The results recommend the determination of pepsinogen I as an indicator of gastroduodenal mucosal changes under therapy with NSAIDs; this determination gives a deciding factor for the gastrolesive potency of an NSAID.
3681073	[Catalase activity of synovial fluid leukocytes in rheumatoid arthritis].	1987 Jun	Catalase activity of rheumatoid synovial fluid measured by a gasometry was higher than that of osteoarthritic fluids, suggesting a possible origin of the catalase activity from synovial fluid leukocytes. Isoelectric focusing polyacrylamide gel electrophoresis of the extract from polymorphonuclear leukocytes (PMN) of rheumatoid synovial fluid exhibited two to four achromatic bands and one dark band of catalase activity. Catalase staining of synovial fluid cells with diaminobenzidine revealed a marked activity in PMN, no or weak activity in monocytes and negative activity in lymphocytes. Catalase scores of the PMN in rheumatoid synovial fluid were lower than those of osteoarthritic fluid and of normal peripheral blood PMN. Ultrastructural localization of catalase activity in leukocytes of rheumatoid synovial fluid was examined by diaminobenzidine staining. Electron dense deposits were observed in granules, probably peroxisomes and in cytoplasm of the PMN and also in microperoxisomes of the monocyte.
2643788	[Malabsorption causing secondary gastrointestinal amyloidosis associated with rheumatoid a	1989 Jan 15	The authors interpret a case report on a secondary amyloidosis involving the whole gastrointestinal tract, and manifested in a rare clinical phenomenon, the malabsorption syndrome. Their histological observations advance the understanding of the pathomechanism of malabsorption.
3067866	Rheumatoid arthritis.	1988 Dec	The results of family and twin studies suggest that RA may result from an interaction between an oligogenic susceptibility and unknown environmental factors. Part of this genetic predisposition is accounted for by genes within the MHC where there is a well-documented association with HLA-DR4. Studies of DR and other MHC variants have shown different associations with particular subgroups. One subgroup is Felty's syndrome where there is a strong association with DR4, as well as associations with DQ-beta and C4B null variants when DR4-matched Felty's and RA subjects are analysed. These DQ-beta and C4B null variants may characterize a single haplotype which is associated with extra-articular disease. A further rheumatoid subgroup characterized by circulating antibodies to native type II collagen, shows an association with HLA-DR3 and 7. Genes on chromosome 14 may also influence susceptibility to RA, probably by interaction with MHC genes and there are different Gm associations for DR4-positive and collagen-antibody-positive rheumatoid subgroups. HLA and Gm markers so far identified only account for a small part of the total genetic predisposition to RA and a third or further loci may also be involved. Possible candidates include T-cell alpha- and beta-chain genes and immunoglobulin light chain genes. One present concept of the genetic predisposition to RA is of several independent immunogenetic pathways each including interactions at two or more loci.